A striking pattern of structure-function relationship has recently emerged from the X-ray crystallographic studies of several NAD-dependent dehydrogenases in spite of distinct differences in the amino acid sequences of these enzymes. The NAD-binding domains in these enzymes exhibit fundamental similarities in their structure as well as in their mode of coenzyme binding. This finding led to the suggestion that the presence of topologically related regions in enzymes of multifarious functions indicates a common evolutionary origin for these enzymes. There is also a concurrent view that the particular folding pattern observed for the NAD-binding domains is just a convenient and energetically favorable way of folding and that convergent evolution is responsible for the commonality of the supersecondary structure-function enzymes. It is the intention of this project to link the structure-function relationship to thermodynamics of interactions of the enzymes and NAD thereby shedding some light on the molecular nature of the structural details involved in enzyme-coenzyme interactions. It is proposed to study the binding of NAD to several dehydrogenases and evaluate the thermodynamic parameters.